Hey Spencer Phillips, Kimmelman Jonathan
Kennedy Inst Ethics J. 2014 Jun;24(2):121-39. doi: 10.1353/ken.2014.0017.
Should first-in-human trials be designed to maximize the prospect of therapeutic benefit for volunteers, prioritize avoidance of unintended harms, or aim for some happy medium between the two? Perennial controversies surrounding initiation and design of early-phase trials hinge on how this question is resolved. In this paper, we build on the premise that the task of early-phase testing is to optimize various components of a potential therapy so that later, confirmatory trials have the maximal probability of informing drug development and clinical care. We then explore three strategies that investigators might use to manage trial risks while optimizing a therapy, using cell therapy for Amyotrophic Lateral Sclerosis (ALS) as an example. We argue that an iterative application of maximin strategies over successive cohorts and trials, which we call the "risk-escalation model," establishes a moral principle that should guide decision-making in early-phase trials.
首次人体试验的设计应该是为了最大化志愿者获得治疗益处的前景、优先避免意外伤害，还是在两者之间寻求某种折衷？围绕早期试验的启动和设计的长期争议取决于这个问题如何解决。在本文中，我们基于这样一个前提，即早期测试的任务是优化潜在治疗方法的各个组成部分，以便在以后的验证性试验中，为药物研发和临床护理提供信息的可能性最大。然后，我们以治疗肌萎缩侧索硬化症（ALS）的细胞疗法为例，探讨研究人员在优化治疗方法时可能用来管理试验风险的三种策略。我们认为，在连续的队列和试验中反复应用极大极小策略，即我们所称的“风险递增模型”，确立了一条道德原则，该原则应指导早期试验中的决策。
